Resistance to the Polyether Ionophore Antibiotic Pandavir (Nigericin) in Two Producing Strains of Streptomyces.

Abstract

In two pandavir (nigericin) producing strains, Streptomyces hygroscopicus 1 55 and Streptomyces albogriseolus 444, an enzyme activity was detected leading to inactivation of the antibiotic in the presence of ATP-Na2. Apparently, the observed inactivation is specific for the antibiotic produced by these strains. The nigericin producing strains were also found to be less permeable to pandavir than their non-producing variants.Organisms which produce antibiotics must be protected from the lethal effects of the latter. For nigericin the following order of ion selectivity was determined: K+>Rb+ >Na+>Cs+>Li+x3). There is considerable evidence that the mechanismof antimicrobial action of the membraneactive complexons involves a decrease of the cytoplasmic K+concentration and also lowering of the cytoplasmic pH. Ribosomal function depends upon K+ions whereas glycolysis and phosphate transport are inhibited at low pH. Microbial membranes contain the ATP synthesizing system and probably the action of these antibiotics lowers AmH, thereby inhibiting phosphorylation and the transport of phosphates. This Batch cultures were grown in YEMEmedium17) for the preparation of S-100 fraction and in AL53 medium1 8) for experiments on cellular impermeability to antibiotics. Batch cultures were grown at 28°C on orbital shakers (220 rpm).Growth of Cells and Preparation of Cell-free Extracts Batch cultures of the two strains and their nonproducing variants were grown in YEMEliquid medium for 40hours. Cells were collected and washed by filtration through WhatmanNo. 1 paper on a Buchner funnel and then twice more by resuspension in RS buffer (10mM Tris-HCl pH 7.6 at 20°C, 10mM MgCl2, 50mM NH4C1, 3mM 2-mercaptoethanol) containing 0.5mM Na2 EDTA,followed by recollection as above.Cell-free extracts were prepared by sonication, followed by treatment with deoxyribonuclease (2/jg/ml) at 4°C for 15minutes and centrifugation at 30,000 x g for 20minutes. The upper 4/5 of the supernatants were layered over 0.33 vol of RS buffer containing 40% (w/v) sucrose and centrifuged at 100,000 x g for 14hours. The

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

“…Nigericin, a K + ,H + -ionophore with antibiotic [10,[22][23][24][25][26], antimalarial [27], anti-Toxoplasma gondii [28] and antiviral [11,29,30] potency, has been considered for the treatment of malignancy [20,31] such as nasopharyngeal carcinoma [22], colorectal cancer [32] and prostate cancer [33]. Nigericin induces apoptosis [14,34,35] with the activation of caspases [14,36,37], dissipation of proton gradients across the mitochondrial membrane [12] and inhibition of autophagy [14].…”